The family Flaviviridae is a group of single, positive-stranded RNA viruses with a genome size from 9-15 kb. They are enveloped viruses of approximately 40-50 nm. Within the Flaviviridae family is the flavivirus genus which includes the prototype yellow fever virus (YFV), the four serotypes of dengue virus (DEN-1, DEN-2, DEN-3, and DEN-4), Japanese encephalitis virus (JEV), Murray Valley encephalitis virus (MVEV), Kunjin virus (KUN), St. Louis encephalitis virus (SLEV), West Nile virus (WNV), Tick-borne encephalitis virus (TBEV), and about 70 other disease causing viruses.
Most flavivirus infections are treated with supportive measures such as anti-pyretics to keep fever down, fluids, antibiotics for secondary bacterial infection, respiratory support as necessary, etc. The use of ribavirin has significant antiviral chemotherapeutic activity against a number of RNA viruses and has been proven to be effective in the treatment of Infuenza virus, Respiratory syncytial virus, Lassa fever virus, and Hanta virus infections. Ribavirin in combination with various interferon drugs is used to treat Hepatitis C virus infections. However, the in vitro and in vivo activity of ribavirin against flaviviruses such as dengue and yellow fever is very weak (Leyssen, De Clercq et al. 2000).
Despite four decades of research effort, safe and effective vaccines against most flaviviruses such as dengue are still not available. Although effective vaccines against yellow fever virus and Japanese encephalitis virus exist, these viruses still cause significant disease worldwide. Efforts to develop an effective dengue vaccine are complicated by the epidemiology of the virus. Although immunity to any given dengue serotype induces lifelong immunity for that particular serotype, a second infection with a different serotype can induce dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS), the severe forms of dengue infection with associated mortality over 20% (Mongkolsapaya, Dejnirattisai et al. 2003).
In view of the severity of the diseases associated with flavivirus infection and their pervasiveness in animals and especially man, there is a need for therapeutic compounds and methods for treating a host infected with a flavivirus.